This application in part discloses and claims subject matter disclosed in our earlier filed pending application, Ser. No. 07/558,082 which was filed on Jul. 25, 1990; now U.S. Pat. No. 5,119,814.
TECHNICAL FIELDThe present invention relates to the medical practice of monitoring arteriovenous oxygen difference. Specifically, the invention relates to an apparatus and method for non-invasively measuring this physiologic parameter by reflectance spectrophotometry.
BACKGROUND ARTIt is necessary to determine arteriovenous oxygen difference, or a-vO2 in order to determine cardiac output, which is an important physiologic parameter, during surgical procedures, post-operative monitoring and the management of critically ill patients. Cardiac output, or C.O. is equal to oxygen consumption, VO2, divided by arteriovenous oxygen difference, a-vO2. The relationship can be stated algebraically as: ##EQU1##
While there are non-invasive methods for determining oxygen consumption, VO2, at the present time, there are only invasive methods for determining arteriovenous oxygen
difference, a-vO2. The non-invasive method for determining arteriovenous oxygen difference of the present method would thus allow cardiac output to be determined without the need for invasive procedures with the attendant risks of infection, bleeding and other trauma. The present invention utilizes the optic disc as the monitoring site. This site was chosen because it has the most accessible peripheral arterioles and venules for non-invasive monitoring.
Prior art using the eye to measure oxygen saturation focused on different portions of the fundus. In U.S. Pat. No. 4,485,820, Flower disclosed a scleral contact lens with a fiberoptic apparatus which measured the hemoglobin saturation of the choroidal arteries. This corresponded to the arterial saturation in, primarily, premature infants. Rather than focusing on the optic disc, Flower utilized the capacity of the eye to serve as an integrating sphere, thereby providing the largest possible surface area to monitor choroidal (arterial) oxygen saturation. Also, Flower did not determine venous oxygen saturation and, therefore, did not determine arteriovenous oxygen difference.
In U.S. Pat. No. 4,877,322, Hill described the use of a collimated beam of light to view specific areas of the fundus, such as the macula, or the optic disc. The ratio of oxyhemoglobin to reduced hemoglobin of these particular areas allows the physician to detect macular degeneration or glaucoma at its early stages.
Novack, in U.S. Pat. No. 4,922,919, measures the oxidative metabolism in ocular tissue by taking advantage of the absorption peak of cytochrome c oxidase. Novack primarily employs an optical probe, which penetrates the ocular body. While Novack describes an alternative apparatus which consists of a contact lens, and subsequently mentions that the invention can also measure desaturated hemoglobin, arteriovenous oxygen difference is not determined. Additionally, Novack does not specifically target the optic disc.
In "The Choroidal Eye Oximeter: An Instrument for Measuring Oxygen Saturation of Choroidal Blood in vivo," IEEE Trans. Biomedical Engineering, Vol. BME-22, No. 3, pp. 183-193, 1975, Laing, R. A., et al., the authors make no distinction between the oxygen saturation of choroidal venous and arterial blood.
As mentioned above, arteriovenous oxygen difference, is a highly useful physiologic parameter. Shepherd et al. designed a spectrophotometer which could analyze the arteriovenous oxygen difference, when venous and arterial blood were pumped from dogs into cuvettes. See, Shepherd, A. P. and C. G. Burgar, "A solid-State Arteriovenous Oxygen Difference Analyzer for Flowing Whole Blood," Amer. J. Physiol., Vol. 232, pp. H437-H440, 1977. More recently, Suga et al. devised an instrument which measures not only arteriovenous oxygen content difference, but arterial and venous oxyhemoglobin saturation as well. See, Suga, Hiroyuki, et al., "Arteriovenous Oximeter for O2 Content Difference, O2 Saturation and Hemoglobin Content", Amer. J. Physiol. 257 (Heart Circ. Physiol. 26): pp. H1712-H1716, 1989. This is an invasive technique that requires cannulation of the subject's artery and vein.
In U.S. Pat. No. 4,305,398, Sawa discloses an eye oximeter for measuring the oxygen saturation of the blood in the fundus of the eye. Sawa recognized that the problem with this type of analysis is the difficulty in discriminating the reflection or absorption of light by the eye fundus blood from the reflection or absorption of light by the various cell layers in the eye fundus. Sawa's approach to solving this problem utilized the phenomenon in which visual pigments in photoreceptor cells may become transparent upon being illuminated by light.
In U.S. Pat. No. 3,565,529, Guyton, discloses a device for providing continuous measurement of the difference between the amount of oxygen in arterial and venous blood. Guyton disclosed an analyzer which determines the oxygen difference in arterial and venous blood. Light of a narrow wavelength is passed through venous blood and arterial blood that has been pumped into cuvettes. This required catheterization of an artery and a vein in order to pump blood through the cuvette and back into the subject's blood stream.
It is known that when red-free light (e.g. green) is shone into the optic fundus, the optic disc, which is free of photoreceptors, appears brighter than the surrounding fundus background. In fact, with the appropriate wavelength of green light, the retinal vasculature appears almost black. See, Paton, D., et al., In: Introduction to Ophthalmoscopy, Edited by B. A. Thomas, Kalamazoo, Mich.: Upjohn Company, 1979, p. 10. Additionally, the maximum absorption wavelength for mammalian rods is 500 nm, and for cones is 562 nm. See, Sharkov, A. V. and Yu A. Matveets, "Ultrafast Processes to Rhodopsins", In: Laser Picosecond Spectroscopy and Photochemistry of Biomolecules, 1987, p. 58.
It has been demonstrated that determination of oxyhemoglobin saturation values can be achieved in vessels as small as 12 microns diameter, using reflectance spectrophotometry. See, Fenton, B. M., et al., "Determination of Microvascular Hemoglobin saturations using Cryospectrophotometry," Amer. J. Physio. 259 (Heart Circ. Physiol. 28): pp. H1912-H1920, 1990. Also, Fenton states that the hematocrit for microvasculature tends to vary from one vessel to another. However, the arteriovenous oxygen difference is independent of hematocrit, at least up to a hematocrit value of 60 to 70%. See, Steinke, J. M., et al., "Role of Light Scattering in Spectrophotometric Measurements of Arteriovenous Oxygen Difference," IEEE TRANS. BIOMEDICAL ENGINEERING, Vol. BME-33, No. 8, pp. 729-734, 1986.
Accordingly, it is an object of the present invention to provide a method and apparatus which can detect arterial and venous oxyhemoglobin saturation in vivo, non-invasively, and atraumatically.
It is another object of the present invention to consistently determine and distinguish between venous and arterial oxyhemoglobin saturation by scanning the optic disc, thereby allowing a determination of the arteriovenous oxygen difference.
It is yet a further object of the present invention to provide a method and apparatus for scanning the optic disc region of the fundus in a linear or curvilinear pattern, thus allowing more than one venule and arteriole pair to be analyzed.
Still another object of the present invention is to provide an apparatus with the capability of sensing the optic disc region of the fundus and accordingly monitoring the optic disc when the optic disc is targeted by the scanning light sources, thus reducing the inaccuracy that results from head and eye movement and that also results from absorbance and reflectance of light by the surrounding fundus tissue layers.
Still yet another object of the present invention is to provide a method and apparatus for determining the arteriovenous oxygen difference in a given patient over a period of time and series of readings thus allowing the patient in question to provide his or her own base line reference.
It is yet another object of the present invention to provide an apparatus for non-invasively determining arteriovenous oxygen difference that is sufficiently mobile to allow examination of multiple patients in separate rooms or facilities.
Other objects and advantages over the prior art will become apparent to those skilled in the art upon reading the detailed description together with the drawings as described as follows.
DISCLOSURE OF THE INVENTIONThe present invention pertains to an optic disc scanner and a non-invasive method for using the optic disc scanner for determining the arteriovenous oxygen difference in the eye. The optic disc region of the ocular fundus was selected as the scanning site for two reasons. First, the fundus is the most readily accessible region of the body for non-invasive vascular studies. Second, the optic disc consistently provides both arterioles and venules in close proximity in animal as well as human subjects. This proximity of vessels allows both arteriolar and venular oxygen saturation to be detected virtually simultaneously without the interference caused by the surrounding fundus tissue layers.
The present method employs a novel way of locating the optic nerve head. Since the retina contains more rods than cones, a tracking beam having a wavelength of approximately 520 nm is utilized. At such a wavelength, reflected signals from vessels and retinal photoreceptors is minimized and reflectance is maximized when this wavelength of light strikes the optic nerve head. The apparatus is constructed such that the scanning beams are focused on a spot within the diameter of the tracking beam point of focus.
In the preferred embodiment, the reflected tracking beam signal, i.e. the image of the surface of the fundus, would be focused on a photodetector which would convert the reflected light into an electrical impulse. A signal processing system would detect an increased reflectance as the tracking beam struck the optic disc and signal the light source control to initiate the scanning sequence. The tracking beam is deactivated by the light source control at the same time that the scanning beams are activated. The scanning beams are activated in a rapid, pulsatile and alternating manner. The scanning sequence lasts for approximately 1/10th of a second. Thus, by employing reflectance spectrophotometry, a tracking beam of the correct wavelength allows the device to distinguish the optic nerve head from the surrounding retina thereby allowing preferred scanning of the arterioles and venules associated with the optic disc.
In an alternate embodiment, an operator would visually see when the tracking beam is focused on the optic nerve head. The operator would then trigger a scanning sequence that would last approximately 1/10th of a second. As in the preferred embodiment, the tracking beam is deactivated by the light source control at the same time that the scanning beams are activated.
The vessels of interest are the retinal arterioles and venules, where they emerge from and overlie the optic disc. In this region, vessel diameter ranges from 100 to 140 microns. Furthermore, as the same fundus region of vasculature is scanned each time, the variability of hematocrit becomes inconsequential at this level.
The optic disc scanner would use a specific set of wavelengths for determining arteriovenous oxygen difference. However, an alternate embodiment could have scanning beams of a different wavelength and would be used to determine the saturation level of carbon monoxide saturation in the hemoglobin and thus monitor the progress of treatment in an instance of carbon monoxide poisoning.
BRIEF DESCRIPTION OF DRAWINGSFIG. 1 is a schematic block diagram of an embodiment of the optical system used for focusing the tracking light beam and the primary and secondary light beams of the present invention.
FIG. 2 is an illustration of the absorption spectra of oxyhemoglobin, deoxyhemoglobin and carboxyhemoglobin.
FIG. 3 is an illustration of the optic disc region of interest of the ocular fundus.
FIG. 4 is a block diagram of the optic disc scanning system of the present invention.
FIG. 5 shows a method for attaching the apparatus of the present invention to the head of the supine subject.
BEST MODE FOR CARRYING OUT THE INVENTIONAn apparatus for scanning the optic disc region of the ocular fundus for determining arteriovenous oxygen difference non-invasively is illustrated generally as 10 in the figures. In FIG. 1, a schematic block diagram of the preferredoptical system 15 above the cornea is shown. Trackingbeam light generator 200, which consists preferably of a light emitting diode (LED), emits trackingbeam 210.Tracking beam 210 is free of red light, i.e. has a wavelength of 589 nm (yellow) or shorter, the preferred light for thetracking beam 210 has a wavelength of 520 nm. It will be recognized by those skilled in the art that either a laser diode which emits at this frequency or a polychromatic light source in conjunction with a spectral isolator, such as a narrow bandpass filter, that would transmit light of this frequency could also be utilized.
Tracking beam 210 is collimated by collimatinglens 270 and then passes throughbeam splitter 230.Tracking beam 210 passes throughaperture 390 inmirror 400 and then enters theeye 50 and forms a spot of illumination having a diameter in the range of approximately 2000 to 2400 microns on thefundus 51. The tracking beam spot of illumination is large enough to envelope theentire optic disc 560. Astracking beam 210 is reflected from the fundus ofeye 50, it strikesmirror 400 and is focused by focusingsystem 410.Tracking beam 210 then is diverted bybeam splitter 420 tophotodetector 450.Photodetector 450 is a narrow bandwidth photodetector that complements the wavelength of the tracking beam, preferably able to detect in the 500-540 nm range. Alternately,spectral isolator 445, which preferably is a narrow band pass filter in the 520 nm range, could be used so as to allow only light of the frequency of the tracking light beam to be detected byphotodetector 450. The signal fromphotodetector 450 is then transmitted to signal processing means 700, in FIG. 4.
As an alert subject's eyes move,tracking beam 210 will "locate"optic disc 560. In green light, theoptic disc 560 reflects a higher intensity signal than the surrounding fundus. When this higher intensity signal is detected bysecond photodetector 450, signal processing means 700 in FIG. 4, by means of a feedback control loop between signal processing means 700 and light source control means 600, activates the primary and secondarylight generators 180 and 190, respectively. Aslight source control 600 activates the primary and secondarylight generators 180 and 190, the trackingbeam light generator 200 is simultaneously deactivated bylight source control 600.Light source control 600 activates primary and secondarylight generators 180 and 190 in a rapid, pulsatile and alternating manner. Minimal eye movement occurs during the scanning interval which is in the range of approximately 10 milliseconds to 1/10th second scan time.
During the aforementioned scan time, aprimary light generator 180 emits aprimary light beam 185 which has a wavelength of light that has a low absorbance by oxyhemoglobin, preferably in the range of approximately 670 nm. Asecondary light generator 190 emits secondarylight beam 195.Secondary light beam 195 is of an isobestic wavelength, such as 803 nm. By using light of an isobestic wavelength, reflectance is independent of oxygen saturation and thus the secondary light beam serves as a reference signal.Primary beam 185 andsecondary beam 195 are focused throughprimary beam lens 280 andsecondary beam lens 290 respectively.
Primarylight beam 185 and secondarylight beam 195strike beam splitter 220.Beam splitter 220 is positioned such thatprimary light beam 185 and secondarylight beam 195 are focused as conjoinedlight beam 205 onmirror 250, Which is attached toactuator 300.
In the preferred embodiment,actuator 300 consists of a galvanometer.Actuator 300 imparts a slight oscillation to mirror 250 about either its longitudinal or latitudinal axis thereby causing conjoinedlight beam 205 to inscribe a small linear path of light onto the optic nerve head. In an alternate embodiment,actuator 300 can consist of piezoelectric components. By this means, it will be recognized that a slight amount of oscillation about both the longitudinal and latitudinal axis ofmirror 250 would result in a curvilinear path of light being transcribed by conjoinedlight beam 205 onto the optic nerve head.
As conjoinedlight beam 205 is reflected fromfirst mirror 250, conjoinedlight beam 205 is focused by focusingsystem 310. From there, conjoinedlight beam 205strikes beam splitter 230.Beam splitter 230 reflects conjoinedlight beam 205 throughaperture 390 inmirror 400 and conjoinedlight beam 205 then enters the cornea ofeye 50. The combined focusing power of the foregoing lenses as well as the subject's own eye result in the conjoined primary and secondary light beams having a diameter of 50 to 100 microns each as they impinge on theoptic disc 560 vasculature. This diameter is calculated to be less than the diameter of the arterioles and venules of this region, FIG. 2. The timing of the alternating pulses is such that a pulse fromprimary light beam 185 and a pulse from secondarylight beam 195 will each strike the same venule or arteriole. As the beams are moved by the action ofactuator 300, a new arteriole or venule will be scanned by a pulse from each of the light beams. The maximum length of this scan pattern is small enough to be contained within the border of theoptic disc 560.
It will be recognized by those skilled in the art, that while a particular light path has been described, the invention should not be limited to this particular light path. This is the preferred optical system for focusing the scanning beams within the focus spot of the tracking beam. Those skilled in the art will recognize that alternate light paths could be constructed such that the scanning beams would be focused within the focus spot of the tracking beam and are thus within the scope of the present invention.
Back-scattered light from the hemoglobin in the illuminatedvenules 520 andarterioles 540, as well as theoptic disc 560 itself, FIG. 3, is reflected back through cornea ofeye 50, FIG. 1,striking mirror 400.Mirror 400 is oriented in a 45° angle to a line perpendicular to theoptic disc 560 rather than the optical axis of the eye. Focusingsystem 410 focusesprimary light beam 185 and secondarylight beam 195 ontothird beam splitter 420 throughspectral isolator 435 and then ontophotodetector 440.Spectral isolator 435 is selected so as to prevent the tracking light beam from strikingphotodetector 440. Preferably,spectral isolator 435 only passes light of the wavelengths ofprimary light beam 185 and secondarylight beam 195.Photodetector 440 is optically focused with the point on the fundus at whichprimary light beam 185 and secondarylight beam 195 strike.
Light source control means 600, shown in FIG. 4 is also critical in preventing the power output of the tracking, primary and secondary light generators from exceeding the safety limit of exposure on the fundus. As mentioned above,light source control 600 also provides the means for emitting light fromprimary light generator 180 and secondarylight generator 190 in a pulsatile, alternating manner. As the light strikes the retinal vessels, the desaturated hemoglobin absorbs and thus reflects light in a quantitatively different way as opposed to saturated hemoglobin. Similarly, the light signal received from the venule is of a different intensity than that of the arteriole. These light signals are detected byphotodetector 440 which transmits the electrical signal to signal processing means 700, where noise is filtered from the signals and the signals are amplified. The signals reflected from arterioles are differentiated from the signals reflected from the venules and the difference between arteriole and venule signals is calculated and information concerning the arteriovenous oxygen difference is displayed ondisplay 750.Display 750 can also display separate intensity values for venous and arterial oxygen saturations.
Scanning at time intervals such as every two to three minutes, allows the physician or operator to detect trends in these saturation values, which is useful either at the bedside or prior to and during surgical procedures.
In an alternate embodiment, the present device can be used to detect carboxyhemoglobin content in the blood non-invasively. Narrow bandwidth laser diodes, such as 5 nm width, can be utilized. These diodes avoid overlap in absorption characteristics of carboxyhemoglobin as opposed to deoxyhemoglobin and oxyhemoglobin. A carbon monoxide detector, such as this, employs two judiciously selected wavelengths for primary and secondarylight generators 180 and 190, respectively. In this alternate embodiment,primary light generator 180 would emit at 568±5 nm, and secondarylight generator 190 would emit at a wavelength that is isobestic for hemoglobin and carboxyhemoglobin, such as 548±5 nm. This wavelength, 548 nm is a triple isobestic wavelength, i.e. the absorption spectra fordeoxyhemoglobin 30,oxyhemoglobin 40 andcarboxyhemoglobin 20 each intersect 25 in FIG. 2 at 548 nm. These two highly specific and narrow-band wavelengths allow signal processing means 700 to distinguish between carboxyhemoglobin and oxyhemoglobin or deoxyhemoglobin via reflectance spectrophotometry. Although this method cannot quantitate carboxyhemoglobin content as the in vitro analyzers can, the present invention permits the user to detect its presence, determine an initial baseline reference and then follow the decline in carboxyhemoglobin with time, as treatment for carbon monoxide poisoning is rendered.
FIG. 5 shows one embodiment for securing the apparatus to a recumbent patients head.Apparatus 10 of the present invention is screwed onto an opaque,periorbital cup 800, which is threaded to receive the device. Once in place, with a snug head band allowing arubber cushion 810 on the rim of the cup to adhere firmly to the face, ambient light is prevented from entering the eye under examination.
While a preferred embodiment has been shown and described, it will be understood that it is not intended to limit the disclosure, but rather it is intended to cover all modifications and alternate methods falling within the spirit and the scope of the invention as defined in the appended claims or their equivalents.